Quantitative assessment of cerebral haemodynamics is essential for reliable estimation of organ state and function. Magnetic resonance imaging (MRI) has shown the ability to provide this information in a noninvasive manner. Especially, arterial spin labeling (ASL) (1-4) is a technique that avoids use of extrageneous contrast agent by using magnetic tagging of inflowing blood spins. (The numerals in parenthesis throughout this patent specification refer to the 14 references cited at the end of the disclosure, all of which are hereby incorporated by reference.) In principle, ASL is capable of providing quantitative estimation of haemodynamics parameters such as cerebral blood flow (CBF) with less theoretical assumptions than other known techniques. ASL typically comprises two phases, one labeling and one control phase. In the labeling phase blood water spins flowing into a slab of interest are inverted upstream by radio frequency (RF) pulses and after an inflow time TI an image of the slab is acquired. In the control phase, the inflowing blood water spins remain uninverted before the image is acquired after TI. The data sets of both phases are subtracted to cancel out signal of stationary tissue and only yield signal of the inflown blood.
There are several techniques which achieve this tagging but usually they can be divided up in two groups: pulsed and continuous ASL. The main difference of these groups is the length of the labeling process that occurs either once for a short period of time (typically less than 50 ms, see FIG. 1a) or over multiple seconds (continuous, see FIG. 1b; and pseudo continuous, see FIG. 1c). It was shown that both groups are useful to estimate local perfusion. However, absolute quantification of CBF is affected by the fact that the time the blood needs to flow to different regions of the imaging slab (so called bolus arrival time, BAT, or arterial transit time, ATT) varies. This is one reason that has kept ASL from becoming a clinical routine tool. In conventional pulsed ASL (PASL) as illustrated in FIG. 1a, the blood is labeled at a specific point in time and in a large spatial region, producing a certain bolus of labeled blood. This bolus will have a certain time of arrival in a downstream imaging voxel of interest. The longer the inflow time TI the larger the amount of labeled blood in this voxel. At a certain point in time the end of the bolus will arrive in the voxel so that the amount of labeled blood within the voxel will remain constant (assuming no relaxation and venous outflow). In continuous ASL (CASL) as illustrated in FIG. 1b, blood is labeled over a longer period of time in a small spatial region. Thus, for a given time (usually several seconds) labeled blood is flowing into the imaging slab. At the time the image is acquired there exists a steady state of the labeled blood in the imaging slab and a larger extent of the vascular tree will be filled with labeled blood. Since the inflow of labeled blood occurs over several seconds no arrival time can be derived from the acquired data. Pseudo-continuous ASL, as illustrated in FIG. 1c, represents a variant of CASL in which the continuous application of the labeling (and control) pulse is broken of into several short time pulses. This will have the same effect as one long pulse as long as all the inflowing blood experience the labeling effect. The pseudo-CASL can be used to reduce SAR problems at higher field strengths.
Several approaches exist to address problems in the above-described approach. They can be categorized in either diminishing the effect of different BAT or somehow measuring BAT and correcting for it. The first goal can be achieved by delaying the image acquisition to longer inflow times (5) or by limiting the length of the bolus by additional saturation pulses upstream the imaging slice a certain time before image acquisition (QUIPSS II (6) and Q2TIPS (7)). However, all these techniques have in common that the signal-to-noise ratio (SNR) of the resulting perfusion images, which is already intrinsically low, is decreased even further. Furthermore, there exists no simple known method to ensure that the requirements for precise parameter estimation are fulfilled, which can be a major obstacle especially in pathologic cases.
Therefore, the most accurate way to measure CBF without dependency on BAT is to acquire a time series with multiple different TI. This allows direct estimation of BAT and correction for it using appropriate theoretical modeling. However, acquisition of time series is very time consuming due to the intrinsic low SNR of ASL. Measurement times of 30 minutes or more are common (e.g. (8)). Recently, a more efficient readout module in combination with ASL was presented (9), which allows reduction of the measurement time while maintaining the same SNR level but the problem still persists.
Another approach for more rapid acquisition of ASL time series is the measurement of more than one data set at different times TI after the labeling RF pulses. This technique is called inflow turbo sampling flow alternating inversion recovery (ITS-FAIR) (10) and is based on a Look-Locker readout in combination with an EPI-readout (REF). The basic idea is to utilize the labeled magnetization for multiple image readouts by using low flip angle RF pulses as excitation pulses. Each of those data sets will have a different TI and principally allows the acquisition of a time series within a single labeling cycle. There is no significant gain in SNR per measurement time compared to conventional ASL since the amount of labeled magnetization remains the same and is just split up. However, for quick evaluation of local BAT this method has proven useful (11). However, this technique is combined with gradient echo based readout modules, for otherwise the refocusing pulses will destroy most of the labeled magnetization.
To capture the dynamic of the inflow of the labeled blood into an imaging voxel of interest, the inflow time TI (time between application of the labeling (or control) pulses and actual image acquisition) is varied between successive experiments, as illustrated in FIG. 2a. To acquire a complete time series of, for example, 20 different TIs, at least 20 complete experiments have to be performed. This is very time-consuming, since several repetitions a necessary to provide sufficient signal. FIG. 2b illustrates a more time-efficient way to acquire time series is the ITS-FAIR technique (10), which uses low flipangle excitation pulses to sample the inflow curve of the labeled blood at several different TI after each labeling/control pulse. In theory, only one experiment is needed to acquire a whole time series of 20 different time points. In practice, however, due to low signal, multiple repetitions are needed and additional saturation effects lead to poor signal in the micro-vasculature.
In continuous ASL (CASL) the amount of labeled blood magnetization present in the imaging slab is greater than in pulsed ASL (PASL) since a labeling RF pulse is applied for a longer period of time. Therefore, in CASL the measured signal is based on a steady-state condition while it originates from a single bolus in PASL. By using more than one labeling RF pulse per cycle in PASL it is possible to increase the amount of tagged blood magnetization. For coronary bolus tagging MR angiography this was presented recently (12) to improve the filling of downstream vessels. The acquired data sets then include signal of labeled blood magnetization which was tagged at different times. However, it is difficult to tell which part of the signal originates from which labeling pulse.